Significantly reduced incidence and improved survival from prostate cancer over 25 years.

BACKGROUND: Prostate cancer (PCa) was the second most frequent cancer and the fifth leading cause of cancer death among men in 2020. The aim of this study was to analyze trends in the incidence, mortality and survival of PCa in Girona, Spain, over 25 years. METHODS: Population-based study of PCa collected in the Girona Cancer Registry, 1994-2018. Age-adjusted incidence and mortality rates were calculated per 100,000 men-year. Joinpoint regression models were used for trends, calculating the annual percentage changes (APC). Observed and net survival were analyzed using Kaplan-Meier and Pohar-Perme estimations, respectively. RESULTS: A total of 9,846 cases of PCa were registered between 1994-2018. The age-adjusted incidence and mortality rates were 154.7 (95%CI: 151.7 157.8) and 38.9 (95%CI: 37.3 -40.6), respectively. An increased incidence of 6.2% was observed from 1994 to 2003 (95%CI: 4.4 -8.1), and a decrease of -2.7% (95%CI: -3.5 -;-1.9) between 2003 and 2018. Mortality APC was -2.6% (95%CI: -3.3 --2.0). Five-year observed and net survival were 72.8% (95%CI: 71.8 - 73.7) and 87.2% (95%CI: 85.9 - 88.4), respectively. Five-year net survival increased over time from 72.9% (1994-1998) to 91.3% (2014-2018). CONCLUSIONS: The analyses show a clear reduction in PCa incidence rates from 2003 on, along with an increase in overall survival when comparing the earlier period with more recent years.

Time trends and survival of marginal zone lymphoma over 25 years in Girona, Spain (1994-2018).

OBJECTIVE: To analyze the incidence, incidence trends, and survival of marginal zone lymphomas (MZLs) in Girona and to describe these indicators based on the location in the case of extranodal MZLs. METHODS: Population-based study of MZL collected in the Girona Cancer Registry, 1994-2018. Sociodemographic data, tumor location, and stage were obtained from clinical records. Crude (CR) and age-adjusted (ASRE ) incidence rates expressed per 100,000 person-years (p-y) were calculated. Joinpoint regression models were used for the trend analysis according to the MZL group. Five-year observed and net survival were analyzed. RESULTS: A total of 472 MZLs were included, 44 (9.3%) were nodal, 288 (61.0%) extranodal, 122 (25.9%) splenic, and the rest (n = 18) MZL, NOS. The CR for the MZL was 2.89 × 100,000 p-y (95% CI: 2.63-3.15), the ASRE was 3.26 × 100,000 p-y (95% CI: 2.97-3.57), and the annual percentage change (APC) was 1.6 (95% CI: 0.5-2.7). The ASRE for nodal MZL was 0.30 × 100,000 p-y (95% CI: 0.22-0.41) and showed an APC of 2.9% (95% CI: -16.4-26.6). For extranodal MZL, the ASRE was 1.98 × 100,000 p-y (95% CI: 1.76-2.23) and the APC was -0.4 (95% CI: -2.0-1.2). The most frequent locations of this type of MZL were the gastric (35.4%), skin (13.2%), and respiratory system (11.8%). The ASRE of the splenic MZL was 0.85 (95% CI: 0.71-1.02) with an APC of 12.8 (95% CI: 2.5-24.0). The 5-year net survival of MZL was 82.1% (95% CI: 76.3-86.5). CONCLUSIONS: This study reveals differences in the incidence and trend of the incidence of MZL according to the subgroup, showing a significant increase in the overall MZL mainly due to splenic MZL type.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Using population-based data to evaluate the impact of adherence to endocrine therapy on survival in breast cancer through the web-application BreCanSurvPred.

We show how the use and interpretation of population-based cancer survival indicators can help oncologists talk with breast cancer (BC) patients about the relationship between their prognosis and their adherence to endocrine therapy (ET). The study population comprised a population-based cohort of estrogen receptor positive BC patients (N = 1268) diagnosed in Girona and Tarragona (Northeastern Spain) and classified according to HER2 status (+ / -), stage at diagnosis (I/II/III) and five-year cumulative adherence rate (adherent > 80%; non-adherent ≤ 80%). Cox regression analysis was performed to identify significant prognostic factors for overall survival, whereas relative survival (RS) was used to estimate the crude probability of death due to BC (PBC). Stage and adherence to ET were the significant factors for predicting all-cause mortality. Compared to stage I, risk of death increased in stage II (hazard ratio [HR] 2.24, 95% confidence interval [CI]: 1.51-3.30) and stage III (HR 5.11, 95% CI 3.46-7.51), and it decreased with adherence to ET (HR 0.57, 95% CI 0.41-0.59). PBC differences were higher in non-adherent patients compared to adherent ones and increased across stages: stage I: 6.61% (95% CI 0.05-13.20); stage II: 9.77% (95% CI 0.59-19.01), and stage III: 22.31% (95% CI 6.34-38.45). The age-adjusted survival curves derived from this modeling were implemented in the web application BreCanSurvPred ( https://pdocomputation.snpstats.net/BreCanSurvPred ). Web applications like BreCanSurvPred can help oncologists discuss the consequences of non-adherence to prescribed ET with patients.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach.

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue.

Incidence of myeloid neoplasms in Spain (2002-2013): a population-based study of the Spanish network of cancer registries.

Comprehensive population-based data on myeloid neoplasms (MNs) are limited, mainly because some subtypes were not recognized as hematological cancers prior to the WHO publication in 2001, and others are too rare to allow robust estimates within regional studies. Herein, we provide incidence data of the whole spectrum of MNs in Spain during 2002-2013 using harmonized data from 13 population-based cancer registries. Cases (n = 17,522) were grouped following the HAEMACARE groupings and 2013-European standardized incidence rates (ASRE), incidence trends, and estimates for 2021 were calculated. ASRE per 100,000 inhabitants was 5.14 (95% CI: 5.00-5.27) for myeloproliferative neoplasms (MPN), 4.71 (95% CI: 4.59-4.84) for myelodysplastic syndromes (MDS), 3.91 (95% CI: 3.79-4.02) for acute myeloid leukemia, 0.83 (95% CI: 0.78-0.88) for MDS/MPN, 0.35 (95% CI: 0.32-0.39) for acute leukemia of ambiguous lineage, and 0.58 (95% CI: 0.53-0.62) for not-otherwise specified (NOS) cases. This study highlights some useful points for public health authorities, such as the remarkable variability in incidence rates among Spanish provinces, the increasing incidence of MPN, MDS, and MDS/MPN during the period of study, in contrast to a drop in NOS cases, and the number of cases expected in 2021 based on these data (8446 new MNs).

Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain.

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR- patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II-III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II-III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Differences in the Impact of COVID-19 on Pathology Laboratories and Cancer Diagnosis in Girona.

INTRODUCTION: The recent COVID-19 pandemic has compromised socio-health care, with consequences for the diagnosis and follow-up of other pathologies. The aim of this study was to evaluate the impact of COVID-19 on cancer diagnosis in Girona, Spain. METHODOLOGY: Observational study of samples received in two pathology laboratories during 2019-2020 (tertiary hospital in Girona and county hospital in Figueres). Date, sample type, and location and morphology were available. Samples were recoded to determine malignancy and grouped by location. Comparisons were made by calendar year and period of exposure to COVID-19. RESULTS: 102,360 samples were included: 80,517 from Girona and 21,843 from Figueres. The reduction in activity in the pathology laboratories in 2020 compared to the previous year was 25.4% in Girona and 27.5% in Figueres. The reduction in cancer diagnoses in 2020 compared to 2019 was 6.8% in Girona and 21% in Figueres. In both laboratories, a decrease was observed in the diagnoses of neoplasms of the lip, oral cavity and pharynx, larynx, colon, rectum and anus, kidney and urinary system, melanoma, and central nervous system. A statistically significant higher probability of a sample received in the pathology laboratory displaying malignancy during COVID-19 was found (Girona: OR = 1.28, 95% CI: 1.23-1.34; Figueres: OR = 1.10, 95% CI: 1.01-1.20) with respect to the COVID-19-free period. CONCLUSIONS: The COVID-19 pandemic has resulted in a reduction in cancer diagnoses by pathology departments that varies according to tumor location and type of hospital. Despite this, the optimization of care resources and the recovery effort have partially reduced the impact of the pandemic in certain neoplasms.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Comorbidities at Diagnosis, Survival, and Cause of Death in Patients with Chronic Lymphocytic Leukemia: A Population-Based Study.

This study aimed to examine the prevalence of comorbidities in patients diagnosed with chronic lymphocytic leukemia (CLL), and to assess its influence on survival and cause-specific mortality at a population-based level. Incident CLL cases diagnosed in the Girona province (Spain) during 2008-2016 were extracted from the Girona Cancer Registry. Rai stage and presence of comorbidities at diagnosis, further categorized using the Charlson comorbidity index (CCI), were obtained from clinical records. Observed (OS) and relative survival (RS) were estimated and Cox's proportional hazard models were used to explore the impact of comorbidity on mortality. Among the 400 cases included in the study, 380 (99.5%) presented at least one comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most common disease. 5-year OS and RS were 68.8 (95% CI: 64.4-73.6) and 99.5 (95% CI 3.13-106.0), respectively, which decreased markedly with increasing CCI, particularly in patients with CCI ≥ 3. Multivariate analysis identified no statistically significant association between the CCI and overall CLL-related or CLL-unrelated mortality. In conclusion, a high CCI score negatively influenced the OS and RS of CLL patients, yet its effect on mortality was statistically non-significant when also considering age and the Rai stage.

Incidence and Survival Trends of Pancreatic Cancer in Girona: Impact of the Change in Patient Care in the Last 25 Years.

(1) Background: We investigated the incidence and survival trends for pancreatic cancer (PC) over the last 25 years in the Girona region, Catalonia, Spain; (2) Methods: Data were extracted from the population-based Girona Cancer Registry. Incident PC cases during 1994-2015 were classified using the International Classification of Diseases for Oncology Third Edition (ICD-O-3). Incidence rates age-adjusted to the European standard population (ASRE) and world standard population (ASRW) were obtained. Trends were assessed using the estimated annual percentage of change (EAPC) of the ASRE13. Observed and relative survivals (RS) were estimated with the Kaplan-Meier and Pohar Perme methods, respectively; (3) Results: We identified 1602 PC incident cases. According to histology, 44.4% of cases were exocrine PC, 4.1% neuroendocrine, and 51.1% malignant-non-specified. The crude incidence rate (CR) for PC was 11.43 cases-per-100,000 inhabitants/year. A significant increase of incidence with age and over the study period was observed. PC overall 5-year RS was 7.05% (95% confidence interval (CI) 5.63; 8.84). Longer overall survival was observed in patients with neuroendocrine tumours (5-year RS 61.45%; 95% CI 47.47; 79.55). Trends in 5-year RS for the whole cohort rose from 3.27% (95% CI 1.69-6.35) in 1994-1998 to 13.1% (95% CI 9.98; 17.2) in 2010-2015; (4) Conclusions: Incidence rates of PC in Girona have increased in the last two decades. There is a moderate but encouraging increase in survival thorough the study period. These results can be used as baseline for future research.

Disparities in the management of cutaneous malignant melanoma. A population-based high-resolution study.

Population-based cancer registry data from three Spanish areas were used to assess the patterns of care and adherence to guidelines for cutaneous malignant melanoma. We included 934 cases diagnosed in 2009-2013. Completeness of the pathology reports, imaging for detecting distant metastasis and the use of sentinel lymph node biopsy (SLNB) were analysed. The proportion of pathology reports that mentioned the essential pathological features required for T staging was 93%, ranging across geographic areas from 81% to 98% (p < 0.001). The percentage of low-risk patients who underwent no imaging studies, as proposed by guidelines, or only chest imaging ranged among areas from 0.6% to 84% (p < 0.001). Of the patients with clinically node-negative melanoma >1 mm thick and no distant metastases, 68% underwent SLNB, varying by area from 61% to 78% (p = 0.017). This study revealed wide geographic variation in different aspects of melanoma care. The use of a standardised structured pathology report could strengthen the completeness of reporting. Improvement strategies should also include efforts to reduce overuse of imaging in low-risk patients and to increase the adherence to guidelines recommendations on the use of SLNB.

Descriptive epidemiology of primary malignant and non-malignant central nervous tumors in Spain: Results from the Girona Cancer Registry (1994-2013).

BACKGROUND: Systematic registration of non-malignant central nervous system (CNS) tumors is a rare practice among European cancer registries. Thus, the real burden of all CNS tumors across Europe is underestimated. The Girona Cancer Registry provides here the first data on CNS tumor incidence and survival trends in Spain for all histological types, including malignant and non-malignant tumors. METHODS: Data on all incident cases of primary CNS tumors notified to the Girona population-based cancer registry from 1994 to 2013 (n=2,131) were reviewed. Incidences rates (IRs) were standardized to the 2013 European population and annual percentage changes (EAPC) were estimated using a piecewise log linear model. 1- and 5-year observed (OS) and relative survival (RS) were also calculated. Results were expressed by sex, age-group, histological subtype and behavior. RESULTS: The overall IR was 16.85 and increased across the period of study (EAPC=+2.2%). The proportion and IRs of malignant (50.2%; IR=9.35) and non-malignant cases (49.8%; IR=9.14) were similar; however, non-malignant tumors were more frequent in women (sex ratio=0.63). The most frequently reported histologies were meningioma (27.6%; IR=5.11) and glioblastoma (22.2%; IR=4.15), which also accounted for the highest and lowest 5-year RS (80.2%; 3.7%, respectively). Globally, 5-year RS was lower in men (42.6% vs. 58.3%, respectively) and in the elderly (64.9% for 0-14years vs. 23.0% for >74years). CONCLUSION: This study presents a comprehensive overview of the epidemiology of malignant and non-malignant CNS primary tumors from the well-established region-wide Girona Cancer Registry (1994-2013). Incidence rates were recovered for all histologies. Survival is still dramatically associated to both age and histological subtype.